Real-world treatment patterns and outcomes in HER2-low, HR+ metastatic breast cancer patients previously treated with endocrine therapy in the United States

BACKGROUND: Up to 60% of metastatic breast cancer (mBC) cases historically classified as human epidermal growth factor receptor 2 (HER2)-negative may be HER2-low, expanding options towards new HER2 targeted treatments. Greater understanding of the current therapeutic journey of this population can help with assessing the potential impact of these novel therapies. METHODS: We conducted a real-world retrospective database study using a United States-based cohort to describe the characteristics, treatment patterns, and outcomes among HER2-low, hormone receptor-positive mBC patients who initiated chemotherapy (index line of therapy [ILOT]) in the metastatic setting either within 6 months of 1 line (L) endocrine therapy (ET) + cyclin-dependent kinase 4/6 inhibitor ("rapid ILOT initiators") or after ≥2L of ET ("index 3L+ group"). RESULTS: Of the 963 patients included, 131 (13.6%) were rapid ILOT initiators and 832 (86.4%) were in the index 3L+ group. Most (80.0%) received single-agent chemotherapy as ILOT, and either a chemotherapy-based regimen (57.0%) or ET ± targeted therapy (26.2%) as a subsequent line (N = 702). Median real-world overall survival (rwOS) from start of ILOT was 18.7 months (95% CI: 17.3, 20.2). Median real-world time to treatment discontinuation or death (rwTTD/D) and real-world time to next treatment or death (rwTTNT/D) were 4.9 (95% CI: 4.6, 5.2) and 5.6 months (95% CI: 5.3, 6.0), respectively. Outcomes were particularly poor among rapid ILOT initiators (median rwOS, rwTTD/D and rwTTNT/D of 15.2, 4.3 and 4.9 months, respectively). CONCLUSIONS: Patients receiving chemotherapy following ET had limited benefit from available treatments, highlighting unmet treatment needs in this population.